AIMS:Following acute myocardial infarction (AMI), pro-angiogenic progenitor cells (PCs) are released from the bone marrow into the circulation and home to the ischaemic site attracted by a chemokine gradient. It is unknown if components of this early homeostatic response might help forecast the long-term clinical outcome. This study investigates if the number and migratory activity of circulating PCs predict adverse events in patients with AMI (clinical trial: NCT01271309). METHODS AND RESULTS:Basal counts and in vitro migratory activity of CD34/CD45/CD133/CXCR4 PCs and serum cytokine levels were assessed during the first 5 days after AMI in a consecutive series of 172 patients. Clinical outcomes of the study were death, repeat AMI, and new-onset heart failure at a 1-year follow-up. The association between PC counts and cytokine levels with the incidence of clinical outcomes was assessed by multivariable regression models. AMI patients who underwent an event showed higher serum stromal cell-derived factor 1α (SDF-1α) levels and reduced spontaneous motility of PCs in an in vitro migration assay when compared with event-free subjects. After adjustment for age, gender, the presence or absence of ST elevation, or diabetes, the percentage of PCs non-migrated towards vehicle or SDF-1α were both independent predictors of death or repeat AMI and new-onset heart failure (odds ratio [OR] = 2, P = 0.015 and OR = 1.90, P = 0.018, respectively). Moreover, serum SDF-1α levels predict adverse events (OR = 3.8, P = 0.007). CONCLUSION:Biomarkers reflecting the migratory activity of circulating PCs may aid the assessment of secondary risk in AMI patients.